Angiogenesis rarely occurs in adult healthy tissues. Vascular endothelial growth factor receptor 2 (VEGFR2) is expressed infrequently and at low levels in normal endothelial cells, as compared to tumor-associated endothelial cells. VEGFR2 expression is 3- to 5-folds higher in tumor vessels than that in normal vessels. Immunohistochemistry in biopsies of cancer patients further confirmed that VEGFR2 expression is significantly elevated in tumor vessels when compared with the vascular endothelium in normal tissues adjacent to the tumor region. Notably, expression of VEGFR2 is greater in high-metastatic tumor vessels than in low-metastatic tumor vessels.
VEGFR2 expression was originally shown to be restricted to the vessels of tumor tissues. However, recent studies have provided evidence that VEGFR2 is also present in malignant tumor cells. Circulating tumor epithelial cells in the blood of breast cancer patients were found to express VEGFR2, and thus such expression is associated with tumor metastasis and prognosis. Therefore, blocking VEGFR2-mediated signaling transduction to concomitantly inhibit tumor endothelial and malignant cells is considered an excellent strategy for the development of anticancer therapeutics.
The results from clinical studies indicate that fully human therapeutic antibodies against VEGFR2 are safe and well-tolerated. They show promise as an emerging therapy for cancer by blocking tumor angiogenesis. Therefore, development of a novel anti-VEGFR2 human antibody with enhanced therapeutic efficacy will benefit cancer patients.